Pill version of obesity drug reduced weight almost 13% in new trial

Novo Nordisk has announced positive results for a new trial of a weight loss pill for obesity. The drug, called semaglutide, is currently sold as injections for treating diabetes and obesity, under the brand names Ozempic and Wegovy. It has exploded in popularity lately for its ability to help people shed weight, sometimes dramatically.

In the new trial, patients on a daily oral dose of semaglutide saw a 15.1% reduction in their weight, compared to 2.4% in the placebo group — meaning additional 12.7% weight loss for those taking the pill.

”The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences,” said Martin Holst Lange, executive vice president for development at Novo Nordisk.

Obesity is tied to a number of serious health risks, including type 2 diabetes, heart disease, stroke, depression, and potentially increased risk of cancer — and obesity rates have been increasing relentlessly for decades. In 2008, the global obesity rate was about 24%; in 2023, it reached 39%, or 3.2 billion people.

A pill form of the same drug as Ozempic and Wegovy reduced patients’ weight by almost 13% compared to a placebo.

A blockbuster: Semaglutide is part of a group of drugs called “GLP-1 receptor agonists,” which are similar to the natural hormone GLP-1 that’s released by the body after you eat. GLP-1 helps the pancreas pump the proper amount of insulin into the blood when blood sugar levels are high, which is why these drugs started out as treatments for diabetes.

But GLP-1 also has another effect, which is to signal to the brain that you’re full.

It’s that second effect that has made semaglutide a household name and a hot topic on social media, as well as causing shortages at pharmacies. It turned out that people who were taking semaglutide for type 2 diabetes also tended to lose a lot of weight, leading to trials testing it as a treatment for obesity.

The injectable drug, sold as Wegovy, was FDA-approved for treating obesity in 2022, and since then it has broken out in a way few medications ever do, getting name-checked by celebrities and debated on social media.

Other GLP-1 agonists, like tirzepatide (currently sold by Lilly as a treatment for type 2 diabetes under the brand name Mounjaro), also cause similarly dramatic weight loss, in the range of 15-20% depending on the dose.

Powered by the clinical results — and word of mouth popularity — the drugs have become a cash cow for Novo Nordisk. Sales totaled $913 million last year, with another $666 million more in the first quarter of 2023 alone, FiercePharma reported. Demand for Wegovy has been so high that Novo has struggled to fulfill demand; the company told FiercePharma in March that it actually backed off marketing the drug because it couldn’t keep up.

While Lilly’s injectable Mounjaro seems to outperform both Novo Nordisk’s pill and another from Pfizer for weight loss, doctors may be more comfortable prescribing pills than injections, BMO capital markets analyst Evan Seigerman predicted to Reuters. Patients could benefit from this larger market and increased options, especially those incapable or uncomfortable with getting weekly injections.

The trial: The phase 3a trial of 50mg oral semaglutide, called OASIS 1, enrolled 667 adults with an average baseline weight of 232 pounds, as well as one or more comorbidities (such as diabetes). Both the group who received the drug and the group who received a placebo were given the same “lifestyle intervention” (essentially, diet and exercise). 

According to Novo, the pill appeared to be “safe and well-tolerated.” The most common adverse events were gastrointestinal, something the oral version shares with the injectible, which both slow down the digestive system. Common side effects include nausea, diarrhea, vomiting, and abdominal pain.

There are rarer but more serious side effects as well, including dehydration, kidney and gallbladder complications, a potential for increased risk of thyroid cancer, and an eye condition called retinopathy, typically caused by diabetes. A small percentage of people in the clinical trials experienced new or worsening retinopathy, which damages blood vessels and can lead to vision loss.

The drugs can also be costly, running easily into the thousands, and may not be approved for weight loss by your insurance. And trials thus far indicate that you need to keep taking the drug in order to keep the weight off.

These considerations need to be stacked against the many health complications of obesity and diabetes.

Novo Nordisk plans to apply for regulatory approval for the pill in the US and European Union in 2023.

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